A whole-animal platform to advance a clinical kinase inhibitor into new disease space was written by Sonoshita, Masahiro;Scopton, Alex P.;Ung, Peter M. U.;Murray, Matthew A.;Silber, Lisa;Maldonado, Andres Y.;Real, Alexander;Schlessinger, Avner;Cagan, Ross L.;Dar, Arvin C.. And the article was included in Nature Chemical Biology in 2018.Synthetic Route of C7H4ClF3O2S This article mentions the following:
Synthetic tailoring of approved drugs for new indications is often difficult, as the most appropriate targets may not be readily apparent, and therefore few roadmaps exist to guide chem. Here, we report a multidisciplinary approach for accessing novel target and chem. space starting from an FDA-approved kinase inhibitor. By combining chem. and genetic modifier screening with computational modeling, we identify distinct kinases that strongly enhance (‘pro-targets’) or limit (‘anti-targets’) whole-animal activity of the clin. kinase inhibitor sorafenib in a Drosophila medullary thyroid carcinoma (MTC) model. We demonstrate that RAF-the original intended sorafenib target-and MKNK kinases function as pharmacol. liabilities because of inhibitor-induced transactivation and neg. feedback, resp. Through progressive synthetic refinement, we report a new class of ‘tumor calibrated inhibitors’ with unique polypharmacol. and strongly improved therapeutic index in fly and human MTC xenograft models. This platform provides a rational approach to creating new high-efficacy and low-toxicity drugs. In the experiment, the researchers used many compounds, for example, 3-(Trifluoromethyl)benzene-1-sulfonyl chloride (cas: 777-44-6Synthetic Route of C7H4ClF3O2S).
3-(Trifluoromethyl)benzene-1-sulfonyl chloride (cas: 777-44-6) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Alkyl chlorides are versatile building blocks in organic chemistry. While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available.Synthetic Route of C7H4ClF3O2S
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics